The rapid development of HIV protease inhibitor drugs between 1989 and 1995 is an early success story of structural biology. Structural biology is concerned with three-dimensional structures of biological molecules. The structure of a molecule crucial in the infectious cycle of HIV was first published in 1989. Only six years later the first drugs targeting this molecule appeared on the market, leading to a dramatic decrease in the death rate from AIDS. In the 15 years since, drug development in general has become increasingly dependent on structural biology. Knowledge of the molecular structure of pathogens often suggests ways to disrupt their function. Compared to the traditional trial-and-error approach this can eliminate years of development time and cut many millions of dollars in development costs. - The predominant method for obtaining molecular structures is X-ray crystallography, which accounts for 87% of all biological structures known today. Long-term large-scale investments by NIH into research facilities of industrial dimensions have increased the number of structures solved per year to nearly 10,000. Unfortunately, certain highly important molecules are difficult to solve with current X-ray techniques. These are the membrane proteins, which are the targets of more than 60% of the drugs on the market. There is an estimated 5,500-7,700 membrane proteins in the human body, but fewer than a dozen structures of these are currently known. This is mainly because membrane proteins are notoriously difficult to crystallize. Without crystals of sufficient size conventional X-ray crystallography is impossible. - Very recently, a new major X-ray technology has emerged that promises to expand the reach to membrane proteins. The construction of the world's first hard X-ray Free Electron Laser (XFEL) was completed in 2009. The first publication of exploratory XFEL work on a membrane protein appeared in February 2011. An XFEL instrument can work with crystals of much smaller sizes than are needed for conventional experiments, sizes attainable even with membrane proteins. However, extracting structural information from an XFEL experiment currently takes many months. In about 28% of all cases, XFEL data processing is faced with ambiguities that prevent the extraction of high-quality results, compromising biological interpretation. For XFEL experiments to realize their full potential, the data processing times need to be decreased by at least two orders of magnitude and the ambiguities need to be resolved. - We have extensive experience developing data processing software for conventional X-ray experiments, with open-source implementations in the Computational Crystallography Toolbox (CCTBX). Building on our internationally recognized expertise and the large set of modular tools in CCTBX, we will implement real-time processing of XFEL data. This will include resolving ambiguities in the data if present, so that high-quality structural information will be within reach for all types of pharmaceutically relevant molecules.